Zhang is a bioengineer focused on developing tools to better understand nervous system function and disease. His lab applies these novel tools to interrogate gene function and study neuropsychiatric disorders in animal and stem cell models. Since joining MIT and the Broad Institute in January 2011, Zhang has pioneered the development of genome editing tools for use in eukaryotic cells – including human cells – from natural microbial CRISPR systems. These tools, which he has made widely available, are accelerating biomedical research around the world.

CRISPR

Zhang leverages CRISPR and other methodologies to study the role of genetic and epigenetic mechanisms underlying diseases, specifically focusing on disorders of the nervous system. He is especially interested in complex disorders, such as psychiatric and neurological diseases, that are caused by multiple genetic and environmental risk factors and which are difficult to model using conventional methods. Zhang’s methods are also being used in the fields of immunology, clinical medicine, cancer biology, and other areas of research. Zhang’s long-term goal is to develop novel therapeutic strategies for disease treatment.

Zhang's work on genome editing traces back to 2010, when he reported the first systematic approach to target specific genes in mammalian cells, using a previously developed system called TALEN. Soon after joining the Broad Institute and MIT, in early 2011 Zhang turned his attention to the CRISPR-Cas system – which researchers in Canada had just demonstrated as being able to create double-stranded breaks in target DNA at precise positions – as a potential tool for improved genome editing. On Oct 5, 2012, Zhang submitted a breakthrough paper which reported the first successful programmable genome editing of mammalian cells using CRISPR-Cas9 (Cong et al. Science 2013). This is now the most-cited paper in genome editing.

Zhang’s CRISPR method for mammalian genome editing has had enormous impact on experimental science and holds great promise for therapeutic applications. His lab continues to refine and improve upon the CRISPR system and to develop novel genome-engineering technologies aimed at perturbing and editing the genome for disease research. In 2015, Zhang developed a simpler and more precise genome editing tool known as CRISPR-Cpf1, and in 2016, the Zhang Lab characterized a new CRISPR system called C2c2 that targets RNA rather than DNA.

Although Zhang is well-known for his pioneering work on CRISPR, he is also widely recognized for developing another breakthrough technology called optogenetics with Karl Deisseroth at Stanford University and Edward Boyden, now of MIT. Nature Methods named optogenetics its 2010 Method of the Year. Zhang demonstrated the utility of optogenetics, in which neuronal activity can be controlled with light, by studying neural circuits in the brain.